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The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism

  • Pharmacology
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Abstract

The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 μmol/L) and FBZ (10 μmol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo dat obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformations.

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Abbreviations

ALD:

aldicarb

ALDSON:

aldicarb sulphone

ALDSOX:

aldicarb sulphoxide

BSA:

bovine serum albumin

ID:

internal diameter

EGTA:

ethylene glycol bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid

FBZ:

fenbendazole

FBZSON:

fenbendazole sulphone

HBSS:

Hanks' balanced saline solution

HPLC:

high-pressure liquid chromatography

LDH:

lactate dehydrogenase

MFO:

mixed function oxidase

NCS:

newborn calf serum

OXF:

oxfendazole

WME:

Williams' Medium E

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Author notes

  1. G. Van't Klooster

    Present address: Div. Pharmacokinetics, Janssen Research Foundation, B-2340, Beerse, Belgium

Authors and Affiliations

  1. Institute of Veterinary Pathology and Hygiene, Faculty of Veterinary Medicine, University of Padova, Agripolis, 35020, Legnaro (PD), Italy

    C. Montesissa

  2. Department of Public Veterinary Health and Animal Pathology, Section of Pharmacology, Faculty of Veterinary Medicine, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia (BO), Italy

    P. Anfossi

  3. Department of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, Utrecht, The Netherlands

    G. Van't Klooster

  4. State Institute for Quality Control of Agricultural Products, RIKILT-DLO, Bornsesteeg 45, 6708 PD, Wageningen, The Netherlands

    M. Mengelers

Authors
  1. C. Montesissa
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Montesissa, C., Anfossi, P., Van't Klooster, G. et al. The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism. Vet Res Commun 20, 449–460 (1996). https://doi.org/10.1007/BF00419182

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